The infectious disease, tuberculosis (TB), is the leading cause of death worldwide from a single human pathogen, claiming more adult lives than diseases such as acquired immunodeficiency syndrome (AIDS), malaria, diarrhea, leprosy and all other tropical diseases combined (Zumla A, Grange J. B M J (1998) 316, 1962-1964). About one third of the world's population is currently infected with Mycobacterium tuberculosis (Mtb), the disease causing agent; 10% of those infected will develop clinical diseases. Although the rate at which people are developing TB has declined, the number of cases continues to increase slowly, according to WHO figures. Hardest hit areas are in the developing world, where poverty, other diseases, and inadequate health care are factors. Killing about 1.6 million people annually, TB is the second leading infectious cause of death worldwide, after HIV/AIDS.
Currently, for effective treatment of TB, a combination of a least the following drugs, isoniazid, rifampin, and pyrazinamide are given to a patient in an initial phase of treatment for 8 weeks, during which the drugs are used in combination to kill the rapidly multiplying population of Mtb as well as to prevent the emergence of drug resistance. This initial phase of treatment is followed by a continuation phase for 24 weeks during which a combination of a least the following drugs isoniazid and rifapentine are given to patients. Such a long combination therapy is not always successful, especially in patients developing drug resistant strains. Also, compliance with the relatively long course of treatment is generally poor. Such non-compliance may lead to treatment failure resulting in development of drug resistance.
In order to control the emergence of drug resistant tuberculosis, the WHO recommends the use of fixed dose combinations (FDC) in the form of tablets which comprise, in the same formulation, two different active principles, namely isoniazid and rifapentine in fixed proportions. FDCs in the form of tablets were previously disclosed.
WO 2007/43542 in the name of SUKA PHARMACEUTICAL CO., LTD discloses a pharmaceutical composition and a kit for tuberculosis treatment. The pharmaceutical composition comprises oxazole compounds, rifapentine and isoniazid, which can be in the form of a tablet.
CN 1717912 in the name of GUANXIN CEN discloses a pharmaceutical composition comprising rifapentine and isoniazid, which can be in the form of a tablet.
CN 185728 in the name of SHUAIHUA MEDICINE SCI TECH CO discloses a sustained release formulation (implant) comprising rifapentine and isoniazid, which can be in the form of a tablet.
However, it is well known by a person skilled in the art that the use of such FDCs may reduce the bioavailability of rifapentine due to an undesirable chemical reaction with isoniazid, especially in the catalytic conditions of the acidic gastric environment (Prasad B. et al. J. Pharm. Biomed. Anal. 2006; 41:1438-1441.).
As such, there remains a need for a stable anti-tuberculosis oral pharmaceutical composition comprising both rifapentine and isoniazid that can prevent the reduction of the bioavailability of the rifapentine and the undesirable chemical reaction with isoniazid.
Applicant has discovered that it was possible to provide such an oral pharmaceutical composition with a satisfactory bioavailability of both active principles by separately granulating the two active principles, and by introducing them in a pharmaceutical composition.